The research proposed in this grant is designed to continue our multidisciplinary investigation of certain behavioral and physiological effects of cocaine in man and to correlate these with the drugs metabolism and selected neurochemical actions of the drug. We are proposing to study changes in sensitivity to the actions of cocaine produced by multiple daily administrations of the drug. Cocaine effects will be studied after both intranasal and intravenous administration. Since this is the normal manner in which cocaine is abused, these studies are of very practical significance. The ability of cocaine to reverse the deterioration of performance caused by sleep deprivation will as well be studied. Changes in amine metabolism associated with sleep deprivation and their interaction with cocaine may help to elucidate the neurochemical basis of the drugs behavioral actions. One of the most important behavioral actions of cocaine is its ability to serve as a positive reinforcer. This action of cocaine will be studied when the drug is administered intranasally and intravenously. Studies of variables which modify the reinforcing actions of cocaine will be carried out. These studies will have great significance for the development of therapeutic procedures for the treatment of cocaine abusers.